circARRDC3 contributes to interleukin‑13‑induced inflammatory cytokine and mucus production in nasal epithelial cells via the miR‑375/KLF4 axis

Abstract

Allergic rhinitis (AR) is a common inflammatory disorder of the nasal mucosa. It is a major risk factor for asthma development, and uncontrolled AR can lead to the worsening of asthma symptoms, which affects the quality of life and productivity of patients. Circular RNAs (circRNA) were reported to be involved in the pathogenesis of AR. The aim of the present study was to investigate the functional role of circRNA arrestin domain-containing 3 (circARRDC3) in AR progression. circARRDC3 knockdown suppressed the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and eotaxin and mucin 5AC (MUC5AC) in IL-13-induced nasal epithelial cells. Moreover, circARRDC3 silencing promoted viability and suppressed apoptosis in IL-13-induced NECs. circARRDC3 targeted microRNA (miR)-375 and negatively regulated its expression. miR-375 inhibition reversed the effects of circARRDC3 knockdown on GM-CSF, eotaxin and MUC5AC expression levels, cell viability and cell apoptosis. In addition, miR-375 inhibited krueppel-like factor 4 (KLF4) expression through direct interaction, and miR-375 overexpression inhibited GM-CSF, eotaxin and MUC5AC expression levels, and cell apoptosis, which was abolished following KLF4 overexpression. In addition, circARRDC3, miR-375 and KLF4 were all dysregulated in the nasal mucosa of patients with AR. miR-375 expression was negatively correlated with circARRDC3 and KLF4 expression, and circARRDC3 expression was positively correlated with KLF4 expression. In conclusion, circARRDC3 contributed to the development of AR by regulating the miR-375/KLF4 axis. These findings may provide novel insights into the pathogenesis of AR.

Peripheral Circular RNA Profiling from Patients with Allergic Rhinitis Identified hsa_circRNA_404013 as a Potential Diagnostic Biomarker

“…But in AR, circRNAs were reported to be involved in the pathogenesis of AR, and their potential role was further highlighted, at the level of AR murine models; the aberrantly expressed circRNAs were considered correlated with miRNAs that are involved in T-cell polarization and activation [16]. Moreover, circRNA arresting domaincontaining 3 contributed to the development of AR by regulating the miR-375/KLF4 axis; highly expressed circHIPK3 and lncGAS5 promoted Th2 differentiation of ovalbumin-induced CD4 + T cells and led to the aggravated nasal symptoms of AR mice that were revealed [36].…”

Mechanism of miR-181a-5p in Regulatory T/T-Helper 17 Immune Imbalance and Asthma Development in Mice with Allergic Rhinitis

“…In this study, we did not specifically explore what cells were infected by lentivirus and produced miR-181a-5p. According to a large number of references [60][61][62][63][64][65], which reported that nasal epithelial cells are the barrier to resist the invasion of external pathogens, which can carry out plasma, siRNA, and miR-NA transduction, regulate the inflammatory response of nasal epithelial cells, and play a major role in AR. Therefore, we speculate that miR-181a-5p may be produced by nasal epithelial cells infected by lentivirus.…”

The Role of Noncoding RNA in Airway Allergic Diseases through Regulation of T Cell Subsets

“…A new study revealed that circHIPK3 was highly expressed in the nasal mucosa of AR mice, and it acted as a sponge for miR-495 and deregulated the transcriptional repression of GATA3, promoting CD4 + T cells to Th2 and secreting cytokines that exacerbate d ovalbumin-induced nasal symptoms [ 158 ]. Investigators identified an essential regulatory role for circARRDC3/miR-375/KLF4z in developing IL-13-induced inflammation in nasal mucosal epithelial cells by accelerating Th2 differentiation [ 159 ]. Currently, studies on the role and mechanism of circRNA in AR are less circRNA expression in AR nasal mucosa and peripheral blood.…”